AbstractAs a major cytoskeleton element of the axon, the breaking of microtubules (MTs) has been considered as a major cause of the axon degeneration. High strain rate loading is considered as one of the key factors in microtubule breaking. Due to the small size of microtubule, the real-time behavior of microtubule breaking is hard to capture. This study employs fully-atomistic molecular dynamics (MD) simulation to determine the failure modes of microtubule under different loadings conditions such as, unidirectional stretching, bending and hydrostatic expansion. For each loading conditions, MT is subjected to extreme high strain rate (10⁸–10⁹ s⁻¹) loading. We argue that such level of high strain rate may be realized during cavitation bubble implosion. For each loading type, we have determined the critical energy for MT rupture. The associated rupture mechanisms are also discussed. We observed that the stretching has the lowest energy barrier to break the MT at the nanosecond time scale. Moreover, the breakage between the dimers starts at ~16% of total strain when stretched, which is much smaller compared to the reported strain-at-failure (50%) for lower strain rate loading. It suggests that MT fails at a significantly smaller strain states when loaded at higher strain rates.